Abstract：
:There is a great need for the development of novel chemotherapeutic agents that overcome the emergence of multidrug resistance (MDR) in cancer. We catalogued the National Cancer Institute's DTP drug repository in search of compounds showing increased toxicity in MDR cells. By comparing the sensitivity of parental cell lines with MDR derivatives, we identified 22 compounds possessing MDR-selective activity. Analysis of structural congeners led to the identification of 15 additional drugs showing increased toxicity in Pgp-expressing cells. Analysis of MDR-selective compounds led to the formulation of structure activity relationships and pharmacophore models. This data mining coupled with experimental data points to a possible mechanism of action linked to metal chelation. Taken together, the discovery of the MDR-selective compound set shows the robustness of the developing field of MDR-targeting therapy as a new strategy for resolving Pgp-mediated MDR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Türk D,Hall MD,Chu BF,Ludwig JA,Fales HM,Gottesman MM,Szakács Gdoi
10.1158/0008-5472.CAN-09-2422subject
Has Abstractpub_date
2009-11-01 00:00:00pages
8293-301issue
21eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-09-2422journal_volume
69pub_type
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